Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux: the FUTURA/OASIS-8 randomized trial
Topic: Anticoagulation in acute coronary syndrome (unfractionated heparin and low molecular weight heparin)
Aim:
- Compare the safety of two unfractionated heparin regimens during PCI in high-risk patients with non–ST-segment elevation acute coronary syndromes initially treated with fondaparinux
Design:
- International, multi-centered, double blinded, parallel-group randomized clinical trial
Treatment:
- Low dose group: unfractionated heparin (IV 50 U/kg bolus (max 10,000 U) irrespective of planned GpIIb-IIIa inhibitor use. No adjustment made based on activated clotting time (ACT)
Control:
- Standard dose group: unfractionated heparin (IV 85 U/kg bolus or 60 U/kg if received planned GpIIb-IIIa (max 10,000 U) , with adjustments made based on ACT
Cohort:
- 2,026 participants
Inclusion criteria:
- New or worsening ischemia, occurring at rest or with minimal activity
- Enrollment within 48 hours of symptom onset
- Planned coronary angiography, with PCI if indicated with 72 hours
- At least 2 of the following: ≥ 60 years; troponin T or I or CKMB above the upper limit of normal; ST-segment depression of ≥ 1 mm in 2 continguous leads, T-wave inversion > 3 mm, or any dynamic ST-segment shifts
Exclusion criteria:
- Contraindication to anticoagulation or angiography
- Patients requiring urgent (<120 minutes) coronary angiography
- 21 years of age or younger
- Treatment of other injectable anticoagulants
- Hemorrhagic stroke within 12 months
- Other indication for anticoagulation
- Women who are pregnant or of childbearing potential
- Life expectancy less than 6 months
- Creatinine clearance less than 20 mL/min
Follow up:
- 30 days
Primary endpoint:
- Composite of peri-PCI major bleeding (48 hours after PCI), minor bleeding, or major vascular access site complications (large hematoma, pseudo aneurysm requiring treatment, AV fistula, or other vascular procedures related to the access site).
Secondary endpoint:
- Composite of peri-PCI major bleeding with death, MI, or revascularization. Others were major and minor bleeding assessed separately; vascular access-site complications; the composite of death, MI, target vessel revascularization; and the components assessed separately; PCI complications, stroke; definite and probable stent thrombosis, all primary and secondary outcomes except major vascular access complications; and PCI related procedural complications, but including catheter thromboses.
Main results:
- Mean age 65 years; 68% of the patients were men.
- Median unfractionated heparin administered were 3800 U (50 U/kg) and 6400 U (85 U/kg) in the low-dose and standard-dose groups, respectively.
- The primary composite outcome occurred in 4.7% in the low-dose group and 5.8% in the standard-dose group (OR: 0.80; CI 0.54-1.19; p=.27).
- Increase in key secondary outcomes (peri-PCI major bleeding, death, MI, and target vessel revascularization at 30 days) in the low-dose group versus standard-dose group (5.8% vs 3.9%) (OR: 1.51; 95% CI, 1.00-2.28; p=.05).
- The secondary outcome of death, MI, or target vessel revascularization was nominally higher in patients receiving low-dose vs standard-dose unfractionated heparin (4.5% vs 2.9%; OR, 1.58; 95% CI, 0.98-2.53; p=.06). In the subgroup of patients without planned GpIIb-IIIa, the difference was greater: 4.9% vs 2.6%, respectively; OR, 1.90; 95% CI, 1.10-3.30 (p=.02).
- Catheter thrombosis was seen in 5 cases (0.5%) in the low-dose group and 1 case (0.1%) in the standard-dose groups (OR, 4.91; 95% CI, 0.57-42.1; P = .15).
- No difference in peri-PCI major bleeding in the low- vs standard-dose groups (1.4% vs 1.2%; OR, 1.14; 95% CI, 0.53-2.49; p=.73), minor bleeding was less in low vs standard group (p=.04)
TAKE AWAY: Patients with NSTEMI ACS undergoing PCI in treated with fondaparinux, should receive ACT-guided standard dose of unfractionated heparin.
